This invention relates to a novel method of preparing 3,5-disubstituted-4-nitroisoxazoles from alpha-nitroketones. In particular, it relates to a method for preparing nitroisoxazoles by catalytic condensation and dehydration of alpha-nitroketones.
Nitroisoxazoles can be prepared by initially forming a 1,2-oxazole and thereafter nitrating the 4-position. One method by which 1,2-oxazoles can be prepared is by cyclization of monooximes of betadiketones with the simultaneous elimination of water. Nitration of the 4-position involves reaction of the 1,2-oxazole with nitric acid suitably in the presence of sulfuric acid at elevated temperatures. While such a two-step method provides some yield of the desired 4-nitroisoxazole, the starting materials are usually highly reactive and frequently form a mixture of products that are not readily separated. Further, the nitration step in many instances is non-selective in nitrating the 4-position, as for example when the oxazole contains acyl or phenyl substituents. When nitration of a phenylisoxazole is conducted, a mixture of aryl and isoxazole nitrosubstituted products are formed. Nitration of, for example, 3-acyl-5-alkylisoxazoles oxidizes the acyl group to a carboxylic acid group. Consequently the method is applicable to the preparation of a limited number of nitroisoxazoles. Each of the aforementioned disadvantages detract from the attractiveness of such processes.
It is therefore an object of this invention to provide a novel method for the preparation of disubstituted 4-nitroisoxazoles.
It is another object of this invention to provide a catalytic method for the preparation of disubstituted 4-nitroisoxazoles.
Yet another object of this invention is to provide a method for preparing disubstituted 4-nitroisoxazoles from alpha-nitroketones in a single step.
Other objects and advantages will become apparent from a reading of the following detailed description and examples.